title: Pharmacokinetics and safety of a 270 mcg kg-1 dose of room temperature stable recombinant activated factor VII in patients with haemophilia.
abstract: Recombinant factor VIIa (rFVIIa), a haemostatic bypassing agent, has been shown to be effective and well-tolerated in patients with haemophilia at standard doses of 90 and 270 mcg kg(-1). A new room temperature stable formulation of rFVIIa was recently developed that was shown to be bioequivalent to and maintain the safety and efficacy profiles of the original formulation at a dose of 90 mcg kg(-1). The aim of this study was to examine the pharmacokinetics and safety of rFVIIa-RT at a 270 mcg kg(-1) dose. The pharmacokinetics and safety of a 270 mcg kg(-1) dose of the newly formulated room-temperature stable recombinant activated factor VII (BHK-rFVIIa-RT) was evaluated in 23 subjects with congenital haemophilia A or B. The pharmacokinetic profile for the 270 mcg kg(-1) dose of BHK-rFVIIa-RT was in line with what was previously observed for the 90 mcg kg(-1) dose. The AUC(last) and C(max) of BHK-rFVIIa-RT at 270 mcg kg(-1) (346.65 h IU mL(-1) and 146.12 IU mL(-1) respectively) were proportionally higher than those observed at the lower 90 mcg kg(-1) dose of BHK-rFVIIa-RT (113.26 h IU mL(-1) and 52.83 IU mL(-1)) demonstrating the dose-dependent nature of BHK-rFVIIa-RT activity. There were no thromboembolic events or related serious adverse events reported with the increased dose of BHK-rFVIIa-RT, and no patients withdrew because of adverse events. This indicates that BHK-rFVIIa-RT was well tolerated at a higher dosage and maintains the favourable safety profile established by rFVIIa. Therefore, the 270 mcg kg(-1) dose of BHK-rFVIIa-RT shows dose-dependent pharmacokinetic effects that do not appear to increase the risk of serious adverse events.
authors.affiliation: Agency for Hemophilia and Regional Reference Center for Inherited Bleeding Disorders, Azienda Ospedaliero Universitaria Careggi, Florence, Italy Novo Nordisk A/S, Medical and Science, Haemophilia, Bagsvaerd, Denmark. m.morfini@dac.unifi.it
authors.forename: M
authors.initials: M
authors.lastname: Morfini
authors.forename: J
authors.initials: J
authors.lastname: Bjerre
mesh_terms: D000328:Adult; D019540:Area Under Curve; D003029:Coagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D015942:Factor VIIa / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006207:Half-Life; D006467:Hemophilia A / Q000188:drug therapy / Q000378:metabolism*; D002836:Hemophilia B / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D013696:Temperature; D055815:Young Adult
chemical_list: D003029:Coagulants; D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa